Objective: To study the role of splenectomy and immunosuppressive drugs in mouse-to-rat cardiac xenograft model. Methods : The animals were divided into 7 groups: group I (n =5)

used as control; group II (n=5)

splenectomy at day 0; group III ( n =6)

treated with cyclosporine A(CsA) 20mg/ kg

every other day from day 0; group IV (n=6)

received leflunomide (Lef) 10mg/ kg/d

from day 0; group V ( n=4)

combined splenectomy with CsA; group VI ( n =5)

added splenectomy and Lef; and group VII ( n=5)

combined splenectomy with Lef and CsA. The sera IgG were determined by ELISA. IgG were detected by immunohistochemistry. Results: ±Splen-ectomy alone significantly prolonged the xenograft survival [(4.401.14) d

P±<0.05 vs group I]. Treatment with splenectomy and CsA significantly improved xenograft survival [(4.750.96)d

P<0.05 vs group I; P>0.05 vs group II]. Combination of splenectomy with Lef significantly prolonged the ±xenograft survival to (8.202.17) d (P< 0.05 vs group I

II

III

IV and V

respectively)

and significantly decreased the serum IgG levels and the IgG deposition in the xenograft (P<0.05). Administration of splenectomy

±CsA and Lef led to a highly significant prolongation of xenograft survival to 8.602.20d

howerer

it had no significant difference compared with group IV. Conclusion: Splenectomy can prolong the cardiac xenograft survival in mouse-to-rat models. Splenectomy has synergistic immunosuppressive effect with Lef to decrease the serum IgG levels and the IgG deposition in the xenograft and effectively prolongs the xenograft survival.